The Center of Excellence of NANOtechnology for Treatment, Understanding, and Monitoring of Cancer (NANO-TUMOR) has been established to perfect a practical nanotechnology base to diagnose, treat, and monitor cancers. Our goal is the development, of a multi-functional "smart mothership" platform that will: (1) evade the reticuloendothelial system and immune system, while attaching specifically to the tumor and its vasculature; (2) assemble a multi-functional complex at the tumor site; (3) deliver payloads of both nanosensors and therapeutics that are activated in situ. The NANO-TUMOR Center has brought together a team of investigators from the University of California, San Diego, Santa Barbara, Irvine, and Riverside campuses, the Burnham Institute and NanoBioNexus. The NANO-TUMOR Center research program is comprised of six interacting projects, each utilizing newly developed and unique technologies that when integrated together will lead to the realization of our goal. The six projects focus on (1) the production of tumor-targeted, non-toxic nanoparticles, (2) the development of a nanoporous micro-platform carrying nanosensors, imaging and therapeutic agents, (3) the creation of tumor-directed amplification systems for sensing and drug delivery, (4) the construction of devices for tumor molecule purification and characterization at a nanoscale level, (5) the application of new computational methods for longitudinal monitoring and analyses of tumor progression and response to therapy, and (6) the in situ assembly and delivery of targeted therapeutics with a smart nanotechnology platform. The Center has been organized using a novel, engineering-type decision and workflow model: Multiple approaches have been proposed to address each project, with go/no go decisions made based on achievement of milestones. The NANOTUMOR project leaders have previously founded more than 20 successful biotechnology companies, with a total market value of over two billion dollars, evidence of their ability to move discoveries to useful applications in the marketplace. The intent of the NANO-TUMOR Center to develop clinically useful platforms is also demonstrated by the strategic role that clinicians from the UCSD Cancer Center, and participants from major corporations (General Electric, Honeywell, Nanogen, Enterprise) will play in evaluating the research.